Dogma vs. data: Rethinking linoleic acid, November/December 2022
By Stacy Kish
In This Section
- Dogma vs. data: Rethinking linoleic acid, November/December 2022
- Improving food packaging, October 2022
- Proteins for meat alternatives: new competition for soy and wheat, September 2022
- Fish heads, fish heads: For biosurfactant production July/August 2022
- Mimicking mother’s milk June 2022
- Three paths forward for sustainable palm oil May 2022
- Is it time to reconsider the role of saturated fats in the human diet? April 2022
- The continued struggle over biofuel feedstocks March 2022
- A new kind of plant breeding February 2022
- The new bio-based surfactant feedstock January 2022
- Lipid role in the immune system November/December 2021
- New essential dietary lipids? October 2021
- Gut Instincts September 2021
- Can computers make better plant-based foods? July/August 2021
- Poisson from a petri dish June 2021
- The latest additions to eco-friendly cleaning May 2021
- Preserving emulsions with plant-based antioxidants April 2021
- Developments in green surfactants for enhanced oil recovery March 2021
- Alternative base oils: a perspective March 2021
- The COVID-19 pandemic, one year later March 2021
- The green machine: commercializing microalgae products February 2021
- Bio-based (edible) oils: feedstock for lubricants of the future January 2021
- The latest on liposomes January 2021
- Fatty acids and athletic performance November/December 2020
- Where are lubricants headed November/December 2020
- New developments in vegetable oil materials science October 2020
- Agriculture at risk: preparing the oilseed industry for a warmer world September 2020
- Science highlights from a cancelled 2020 AM&E July/August 2020
- Managing your career in times of change June 2020
- Lipidomics comes of age May 2020
- Minimally processed oils April 2020
- The high-throughput frontier March 2020
- Nurturing innovation: how AOCS industries are fostering progress February 2020
- The trouble with studying omega-3s and the brain January 2020
- Understanding pulse anti-nutrients January 2020
- Digitizing manufacturing: how companies are using data to improve production November/December 2019
- Weaving together genetics, epigenetics, and the microbiome to optimize human nutrition October 2019
- Taking the cream out of ice cream September 2019
- Science highlights from St. Louis July/August 2019
- Biotechnology conquers consumer goods June 2019
- Cool characterization methods and where to find them May 2019
- Fermentation, the new protein supply chain April 2019
- Oleogels for drug delivery March 2019
- The complexity of clean-label cosmetics February 2019
- Rethinking plastic packaging January 2019
- Trends in synthetic and natural antioxidants for shelf life extension of meat and meat products November/December 2018
- The icing on the cake October 2018
- Enhancing oxidative stability and shelf life of frying oils with antioxidants September 2018
- Under arrest: investigating factors that govern partial coalescence July/August 2018
- Unconventional Oils June 2018
- Beauty from within May 2018
- Pulses rising April 2018
- Lessons learned from Hurricane Harvey March 2018
- Clean meat February 2018
- What makes your shortening suitable for fancy croissants, puff and Danish pastry? January 2018
- Strategic role of peanuts in sustainable global food security November/December 2017
- Science beyond borders: international student exchange October 2017
- Clean label: the next generation September 2017
- Science snapshots from Orlando July/August 2017
- Five new AOCS methods June 2017
- The whys and wherefores of life-cycle assessment May 2017
- China’s evolving edible oils industry April 2017
- The mysterious case of the arsenolipids March 2017
- Red palm oil February 2017
- The Highs and Lows of Cannabis Testing October 2016
- Chia: Superfood or superfad? January 2017
- Generational training divide November/December 2016
- Storage stability of roasted nuts and stabilization strategy using natural antioxidants September 2016
- Good vibrations: online and at-line monitoring of edible oils with vibrational spectroscopy July/August 2016
- Benchtop NMR spectroscopy for meat authentication June 2016
- Coconut oil boom May 2016
- Sink or swim: fish oil supplements and human health April 2016
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- Prescribing dietary fat: therapeutic uses of ketogenic diets February 2016
- Organogels of vegetable oil with plant wax January 2016
- The power of peptides November/December 2015
- Separation anxiety: membrane cleaning in the 21st century October 2015
- Using direct solid phase extraction to analyze persistent organic pollutants in oily food samples September 2015
- Big fat controversy: changing opinions about saturated fats June 2015
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- 1970s fish oil study criticized January 2015
- Developing a high-performance, low-streak degreaser November/December 2014
- Detection, monitoring, and deleterious health effects of lipid oxidation November/December 2014
- Modified protein mimics taste and texture of fat October 2014
- Development of the first efficient membrane separations of cis fatty acids October 2014
- Regulatory updates on FSMA and combustible dust September 2014
- How enzymes are transforming manufacturing September 2014
- Two advances in biodiesel technology July/August 2014
- 2014 AOCS Annual Meeting & Expo July 2014
- Peanut genome sequenced June 2014
- A customized approach to frying oil June 2014
- Omics reveals subtle changes in carbon flux that lead to increased oil biosynthesis in oil palm May 2014
- Cannabis testing: a review of the current landscape May 2014
- Industrial hemp gaining traction April 2014
- Emulsions: making oil and water mix April 2014
- Lipid co-oxidation of proteins: One size does not fit all March 2014
- FSMA marches on March 2014
- Disruptive technology? Walmart’s “green” product line may signal a big change February 2014
- Pathways to novel chemicals February 2014
- Specialty lipids in pet nutrition January 2014
- EFSA releases preliminary report on occurrence of 3-MCPD in food January 2014
- Seven new biobased surfactant technologies November/December 2013
- Do oil color scales make you see red . . . or yellow? November/December 2013
- Shortage leads to green route to olefins October 2013
- Sesamol: a natural antioxidant for frying oil September 2013
- FSMA update September 2013
- Patent rights and biotech seeds July August 2013
- The other vitamin E July 2013
- Frac fever heats up June 2013
- Fat fight: Catch-22 for Western oleochemicals? June 2013
- Health and Nutrition News April 2013
- FDA asks for fees from industry to fund FSMA June 2013
- What does it take to start a biodiesel industry? April 2013
- What’s in a Claim? Would a Food Not Labeled “Natural” Taste as Sweet? March 2013
- Regulatory overview March 2013
- The preservative wars February 2013
- Plants producing DHA February 2013
- Swift response to paper on feeding GMO corn, glyphosate January 2013
- AOCS: supporting international standards January 2013
- TSCA and the regulation of renewable chemicals July August 2013
- trans Fatty acid content of foods in China January 2013
- A novel green catalytic process for biodiesel production from Jatropha November/December 2012
- The America Invents Act: Groundbreaking US patent law changes are here November/December 2012
- “Super Phos” esters: the key to higher-performance products November/December 2012
- Advances in field-portable mass spectrometers for on-site analytics October 2012
- EFSA sets upper intake level for LC-PUFA October 2012
- Malaysia: economic transformation advances oil palm industry September 2012
- High-oleic canola oils and their food applications September 2012
- Using enzymes to prepare biobased surfactants July/August 2012
- Oilseeds: at the center of food, water, and energy security July/August 2012
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- Hydrocolloids get personal June 2012
- The secrets of Belgian chocolate May 2012
- Plants “remember” drought, adapt May 2012
- The power of mass spectrometry in the detection of fraud April 2012
- Oil in biomass: a step-change for bioenergy production? April 2012
- The Future of LAB March 2012
- World supplies of rapeseed and canola likely to remain tight in the 2012/13 season March 2012
- Methods for differentiating recycled cooking oil needed in China February 2012
- Supercritical fluid-based extraction/processing: then and now February 2012
- Singapore: the place to be in 2012 February 2012
- The Food Safety Modernization Act and its relevance to the oilseed industry February 2012
- Oilseeds in Australia January 2012
- Hydrogen peroxide in home-care formulations November 2011
- A new generation of renewable fuels is on the horizon November 2011
- Omega-3 fatty acids: $13 billion global market October 2011
- Soy and breast cancer October 2011
- EU approves food labeling rules September 2011
- IOM panel recommends tripling vitamin D intake: Panel’s conservative approach receives criticism September 2011
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- Maybe we don’t know beans March 2011
- Short- and long-term price forecasting for palm and lauric oils February 2011
- New 3-MCPD (glycidol ester) method February 2011
- Regulatory issues associated with the international oils & fats trade January 2011
- Point-counterpoint on UC Davis olive oil report January 2011
- Biomass--The next revolution in surfactants? December 2010
- One person’s response to a high omega-6 diet November 2010
- Crop residues as feedstock for renewable fuels November 2010
- Universal detectors for determination of lipids in biodiesel production October 2010
- New very long chain fatty acid seed oils produced through introduction of strategic genes into Brassica carinata October 2010
- Surfactants based on monounsaturated fatty acids for enhanced oil recovery September 2010
- Questioning the virginity of olive oils September 2010
- Dietary guidelines report released August 2010
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- First high-GLA safflower oil on market June 2010
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- Oilseeds of the future part 3 July 2009
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- Oilseeds of the future: Part 2 June 2009
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- Raw material sources for the long-chain omega-3 market:Trends and sustainability. Part 3. May 2009
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- Raw material sources for the long-chain omega-3 market: Trends and sustainability. Part 2. April 2009
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- Raw material sources for the long-chain omega-3 market:Trends and sustainability. Part 1. March 2009
- A convenient way to increase legume intake February 2009
- Vitamin E’s safety controversy January 2009
- Universal mechanism of aging uncovered? January 2009
Humans have evolved to eat a variety of foods. No one component is entirely bad or entirely good. Many diets popular today, approach nutrition through a narrow, simplified lens. Every decade one component of our diet is placed center stage as the villain that is responsible for all of our woes. In recent decades, the spotlight has been turned on fats.
- Fats play a critical role in nutrition but are often viewed through the narrow lens of the omega-6: omega-3 ratio. The western diet skews the ratio toward omega-6, which has been maligned for different health conditions, from chronic heart disease to diabetes.
- New research confirms linoleic acid, an omega-6 fatty acid, has many positive implications on human health, including promoting the accumulation of lean mass, the proper functioning of the mitochondria, and the ability to stave off heart disease, diabetes, and fatty liver disease.
- Martha Belury, the Carol S. Kennedy professor of human nutrition in the Department of Human Sciences at the Ohio State University, in Columbus, Ohio, USA, has followed the data throughout her research career, shifting her focus from omega-3 to the health benefits of omega-6 fatty acids.
- Because of the strong evidence for linoleic acid as a protective fat for many chronic diseases, the omega-6:omega-3 ratio is now considered a misleading or outdated method of categorizing dietary fats and has been replaced by the omega-3 Index, which has been shown in clinical studies to predict coronary heart disease more accurately.
Fat is essential, providing a source of energy and a feeling of satiety. There are essential fatty acids that humans cannot produce, including linoleic acid (omega- 6) and alpha-linolenic acid (omega-3). Both fatty acids are obtained from the food we eat and play a critical role in major cellular events, including metabolism, inflammation, cell differentiation, and cell death. Some dietitians and nutritionists have advocated for eating an equal amount of omega-6 and omega-3 fatty acids, resulting in a 1:1 ratio. This diet is presumed to mimic the ancient human diet, though no definitive data supports what early humans actually ate consistently. The modern American diet ranges from a value of 10:1 to 15:1.
The overarching nutritional message has been that the modern diet suffers from an “omega imbalance.” The imbalance is a ‘concern,’ because omega-6 fatty acids, which skews the index to higher numbers, have been assumed to promote poor health outcomes and disease, including increased ‘bad’ cholesterol (LDL), inflammation, and coronary heart disease. Surprisingly, no randomized controlled clinical trials actually support any of these claims. (https://doi.org/10.1007/s11883-006-0019-7).
The concept of the omega-6:omega-3 ratio is “flawed and unhelpful,” says William Harris, professor of basic biomedical sciences at the University of South Dakota, in Vermillion, South Dakota, USA.
Harris is the founder and president of the Fatty Acid Research Institute, a non-profit research and education organization created to further the study of fatty acids and disease. To expand on Harris’s point, measuring the ratio is difficult because each fatty acid appears as various species in different ratios in different reservoirs in the body. According to Harris, this simple metric has “both theoretical and practical complications” that create fundamental misunderstandings that have cascaded through the field. He has published numerous articles describing the lack of scientific validation to support using this ratio as an indicator of healthful diet (https://doi.org/10.1016/j.plefa.2018.03.003).
Martha Belury, Carol S. Kennedy professor of human nutrition in the Department of Human Sciences at the Ohio State University, Columbus, Ohio, USA, concurs with Harris’s assessment. She believes it is time to move away from the omega-6:omega-3 ratio and re-evaluate the benefits of the much maligned omega-6 fat.
“Science and health are short-changed if we oversimplify,” said Belury. “While omega-3 has an important role in health, omega-6 has a pivotal role to play as well. This is an important message for consumers and practitioners.”
LINOLEIC ACID: THE VILLAIN OF MODERN GLUTTONY?
Belury began her career arguing for omega-3 fatty acids. One of her studies during her doctoral program aimed to evaluate the protective nature of omega-3 fatty acid in a mouse model for skin cancer. As is standard, she set up a control, in this case an omega-6 fatty acid, to compare the results. To her surprise, the results showed omega-6 fatty acid offered unanticipated protection too.
“Dogma exists in science like it does everywhere and sometimes scientists are blind to results that go against what they anticipate,” said Belury. “Shifting the paradigm is difficult. It requires time, patience, and money.”
Belury was fortunate to have an advisor and mentor who encouraged her to pursue the truth no matter where the data took her. She is now confident in one thing—lipids are not a simple or straight forward story.
Belury says nutrition does not operate like a binary system where one fat is good and one is bad. Rather, fatty acids require a more nuanced approach to illustrate the complexity of the natural world. Her research follows a series of clues, supported by studies around the world, to unravel the complex interactions this fatty acid has in human health.
WHEN RESEARCH COUNTERS CONVENTIONAL WISDOM
Linoleic acid is the most common form of omega-6 fatty acid. It is found in vegetable oils, nuts, seeds, and animal products. As the American diet has evolved, linoleic acid, a component of soybean and many other vegetable oils, has increasingly found its way into processed foods. Today, soybean oil accounts for as much as 45 percent of the dietary intake of linoleic acid in the United States (https://doi.org/10.3945/an.113.003772).
In 2014, a team of researchers from Uppsala University and the Karolinska University Hospital in Sweden published the results of the Lipogain clinical trial (https://clinicaltrials.gov/ct2/show/NCT01427140). The double-blind, randomized, seven-week study examined the role of two dietary fats on body fat accumulation and ectopic fat storage. The study while small—only 39 participants were enrolled—revealed that the type of fat consumed has a powerful impact on liver fat accumulation, fat distribution, and body composition. Participants were fed either muffins baked with linoleic-rich sunflower oil or palm oil, a saturated fatty acid that is commonly used in food around the world. While both groups gained weight, the group fed the palm oil muffins gained more liver fat, total fat, and abdominal fat. The group fed the sunflower oil-rich muffin gained more lean tissue. The study supported much of Belury’s research on the positive health outcomes of linoleic fatty acid.
Linoleic Acid Revs Up the Mitochondria
New research is finding that mitochondrial dysfunction may play a role in many diseases, from diabetes to Parkinson’s disease. Mitochondria are critical in the cell, producing ATP that powers all activities as well as generating heat and regulating cell death. Healthy mitochondria are lined with tetralinoleoyl-cardiolipin. Unlike other phospholipids that are constructed with two chains of fatty acids that could include linoleic acid, palmitate or oleate, the structure of tetralinoleoyl-cardiolipin consists of four linoleic fatty acid chains. The unusual structure lies in its bacterial origin.
“Cardiolipin is a very understudied fat,” said Genevieve Sparagna, research assistant professor at the University of Colorado Anschutz Medical Campus in Aurora, Colorado, USA, who has worked with Belury on previous research projects. “It is derived from ancient bacterial phospholipids, so it is unique,” she says.
The four fatty acids are connected via two phosphates linkages at either end of a gycerol backbone. This construction produces a super strong mesh with a chevron- like pattern. The mesh forms the scaffold of the electron chain transport super complex that allows electrons to flow through the mitochondrion creating ATP energy without leaking.
Advances in technology have opened new opportunities to study the mitochondrial function beyond the normal process of monitoring changes in oxygen consumption. Subtle changes in the cardiolipin mass are detected using mass spectrometry.
According to Sparagna, other fatty acids can replace linoleic acid in the tetralinoleoyl-cardiolipin mesh inside the mitochondrion. These substitutions reduce the efficiency of the ATP creation and increase electron loss. As a result, the mitochondrion provides less energy for the cell.
By looking at the mass of the mitochondrion, it is possible to determine exactly which fatty acids are being substituted on the tetralinoleoyl-cardiolipin curtain. This information opens opportunities to understand why the mitochondria is not performing optimally. Sparagna is now running these tests on peripheral blood mononuclear cells—immune cells with a single, round nucleus that originate in bone marrow, rather than the traditional but more invasive skeletal muscle tissue obtained with a biopsy.
In 2020, Belury published the results of a similar study that measured the effect of linoleic acid on measurements associated with body fat and metabolism on 15 post-menopausal, nondiabetic women with metabolic syndrome (https://doi.org/10.1093/cdn/nzaa136). During menopause, estrogen plummets. A woman’s body composition changes, leading to weight gain around the abdomen. Metabolic syndrome is characterized by abdominal obesity, low good cholesterol (HDL), and elevated triglycerides, glucose, and blood pressure. These conditions increase the risk for heart disease and diabetes. During the 16-week study, participants received two teaspoons of linoleic acid-rich vegetable oil per day.
The study results showed that supplementing the diet with linoleic oil increased total and high molecular weight adiponectin concentration, a hormone released by fat tissue that helps cells in the body use blood glucose more effectively. The linoleic oil also increased the concentration of oxylipins, a family of oxygenated products produced by fatty acids that may play a role in mitigating cardiovascular disease. These findings suggest linoleic supplements deserve greater scrutiny in patients with metabolic syndrome.
Belury was curious if the mitochondria could be a target of linoleic acid. To delve deeper into the role of linoleic acid on mitochondrial function, her lab examined dietary fat in a mouse model. For 25 weeks, mice were fed a lard diet that mimicked the fat intake pattern in the western diet or one rich in linoleic-rich safflower oil. Following a series of lipodomic analyses, they found that the mice fed the linoleic-rich diet increased the concentration of tetralinoleoyl-cardiolipin, the phospholipids lining mitochondria.
An earlier study found rats bred to have heart failure responded positively to a diet supplemented with linoleic acid. Cardiac mitochondria are especially powerful organelles that supply the energy needed to keep the heart beating 24 hours a day, seven days a week. The linoleic-rich diet supercharged the mitochondria compared to carbohydrateor lard-rich diets. The heart-challenged rats should have died young, but the linoleic acid intervention allowed them to live into old age. More surprisingly, the rats responded to the change in diet in less than 24 hours (https://doi.org/10.1161/HYPERTENSIONAHA.108.114264).
This previous finding provoked Belury to continue her mitochondrial studies in humans. Her team developed a blood test using protocols published by her peers to evaluate mitochondrial function. Healthy mitochondria convert fat into energy efficiently. As a result, a person with healthy mitochondria have less fat tissue, more lean mass, and respond to insulin more effectively. Belury confirmed these findings in a small study where participants were given either a cookie made with linoleic-rich safflower oil or a cookie rich in oleic oil. They found the linoleic-rich diet increased the concentration of tetralinoleoyl-cardiolipin in blood samples. The oleic-rich diet increased oleic-rich cardiolipin, which had a blunting effect on mitochondrial function.
To pursue these initial findings further, Belury constructed the WELL (Weight, Energy, Lipids & the Liver) Study. The on-going, 18-week clinical intervention aims to evaluate the role of two dietary fats—palm oil and soybean oil—on liver fat and abdominal fat. According to Belury, 30 percent of Americans have non-alcoholic fatty liver disease. This disease sets up a detrimental positive-feedback loop. As the liver accumulates fat, it becomes insulin resistant, allowing nonlipid precursors to produce more fatty acids. The more fat the liver accumulations, the worse the health outcomes. Forthcoming results from the WELL Study could provide additional information about the protection conferred by omega-6 fatty acids (https://clinicaltrials.gov/ct2/show/NCT05199948).
FROM A RATIO TO AN INDEX
Some researchers are still confounded by the notion that omega-3 and omega-6 were ever embroiled in a zero-sum competition. Both are components of a healthful diet and play an important role in the body and human health. While many nutritionists now see the error in the simplicity of the omega-6:omega-3 ratio, the concept has become enmeshed in the conventional dietary narrative. This concept has also influenced research funding trends, stifling researchers’ ability to explore the health implications of fatty acids on a variety of diseases. However, a more reliable indicator has emerged—the omega-3 index, a measure of the weight percent of total red blood cell membrane fatty acids.
The omega-3 index focuses on the sum of two omega-3 fatty acids: eicosapentaenoic acid and docosahexaenoic acid. An optimal omega-3 index is 8 percent or higher. The index has been shown in multiple observational and cohort studies to be a better predictor for coronary heart disease, sudden cardiac death, and impaired cognitive function (https://doi.org/10.1016/j.atherosclerosis.2017.05.007). The omega-3 index is also easier to measure than the omega-6: omega-3 ratio. Similar to the A1C test that is used to evaluate the glycemic status for patients with diabetes, the omega-3 index can be measured with a simple blood test.
Beyond the omega-6:omega-3 ratio or omega-3 index, the science provides a clear and powerful argument for the benefits of linoleic acid. It is now time for fellow researchers, practitioners, reporters, and funding agencies to take a more holistic approach to fat and begin the slow shift in how we view this critical component of our diet. In the future, Belury wonders if there will also be a place for a Recommended Dietary Allowance for linoleic acid.
“Fatty acids are among the simplest molecules in nutrition, but there is still so much we do not understand,” said Belury. “My hope is that in the future researchers can study linoleic acid to understand its role in human health.”
About the Author
Stacy Kish is a science writer for INFORM and other media outlets. She can be contacted at email@example.com